HIPAA Effects on Health Research and PBM Functions in Drug Utilization Review

■■ A Closer Look at Pharmacy Technicians An important component of discussions around the pharmacy workforce shortage issue is the appropriate use of technicians in various practice settings, the extent to which technicians are licensed and regulated, and the level of training necessary for technicians. Simultaneously, the growth of the number of pharmacy technicians presents a boon to the profession and a substantive challenge. On one hand, the use of technicians helps to address the dramatic shortage of pharmacists that exists in today’s marketplace. That shortage is expected to increase. Technicians are being used in a variety of ways in many different venues. As referenced in the “2002 White Paper on Pharmacy Technicians: Needed Changes Can No Longer Wait,” it is noted that there are as many as 250,000 technicians operating in the United States. Functioning under the management of licensed pharmacists, technicians can perform repetitive, rote tasks that free pharmacists to deal with issues that necessitate their extensive training and expertise. In this manner, they provide a definite boon to the profession. On the other hand, the lack of standardization in the preparation requirements for technicians is an Achilles’ heel for the profession. While the profession vests technicians with the provision of direct service to the public, training and education requirements vary dramatically from state to state. In some jurisdictions, technicians must have successfully completed comprehensive education programs. Others mandate that technicians become certified through the Pharmacy Technician Certification Board. Employers often mandate in-service training to introduce the new technician to their roles, but this is at the discretion of the employer, creating great variations. Alarmingly, in some states, all that is required is a modest registration fee, without attestation to training of any sort. The 2002 white paper is an update of a white paper on pharmacy technicians that was originally published by the American Pharmaceutical Association and the American Society of HealthSystem Pharmacists in 1996. The Council on Credentialing in Pharmacy authorized an update to the piece to reflect the dynamic changes that have occurred in the intervening years. The Council on Credentialing in Pharmacy is dedicated to credentialing programs in pharmacy that meet established standards of quality that will contribute to significant improvement in the pharmaceutical care of patients and the overall public health. The council strives to introduce standardization into postlicensure training for pharmacists and training for technicians. Its members include: • Academy of Managed Care Pharmacy • American College of Apothecaries • American Council on Pharmaceutical Education • American Society of Consultant Pharmacists • Board of Pharmaceutical Specialties • Pharmacy Technician Certification Board • American Association of Colleges of Pharmacy • American College of Clinical Pharmacy • American Pharmaceutical Association • American Society of Health-System Pharmacists • Commission for Certification in Geriatric Pharmacy Similar to the individual pharmacist-supervisor bearing the responsibility for the technician’s work product, the profession has a responsibility to assure that technicians are properly educated and trained to undertake the work assigned to them. Without standardization of professional training requirements for technicians, the profession is deficient in meeting its responsibility to society. The 2002 white paper is mandatory reading for anyone concerned with this issue. It clearly lays out the challenge to the profession.


■■ A Closer Look at Pharmacy Technicians
An important component of discussions around the pharmacy workforce shortage issue is the appropriate use of technicians in various practice settings, the extent to which technicians are licensed and regulated, and the level of training necessary for technicians. Simultaneously, the growth of the number of pharmacy technicians presents a boon to the profession and a substantive challenge.
On one hand, the use of technicians helps to address the dramatic shortage of pharmacists that exists in today' s marketplace. 1 That shortage is expected to increase. Technicians are being used in a variety of ways in many different venues. As referenced in the "2002 White Paper on Pharmacy Technicians: Needed Changes Can No Longer Wait," it is noted that there are as many as 250,000 technicians operating in the United States. Functioning under the management of licensed pharmacists, technicians can perform repetitive, rote tasks that free pharmacists to deal with issues that necessitate their extensive training and expertise. In this manner, they provide a definite boon to the profession.
On the other hand, the lack of standardization in the preparation requirements for technicians is an Achilles' heel for the profession. While the profession vests technicians with the provision of direct service to the public, training and education requirements vary dramatically from state to state. In some jurisdictions, technicians must have successfully completed comprehensive education programs. Others mandate that technicians become certified through the Pharmacy Technician Certification Board. Employers often mandate in-service training to introduce the new technician to their roles, but this is at the discretion of the employer, creating great variations. Alarmingly, in some states, all that is required is a modest registration fee, without attestation to training of any sort.
The 2002 white paper is an update of a white paper on pharmacy technicians that was originally published by the American Pharmaceutical Association and the American Society of Health-System Pharmacists in 1996. The Council on Credentialing in Pharmacy authorized an update to the piece to reflect the dynamic changes that have occurred in the intervening years.
The Council on Credentialing in Pharmacy is dedicated to credentialing programs in pharmacy that meet established standards of quality that will contribute to significant improvement in the pharmaceutical care of patients and the overall public health. The council strives to introduce standardization into postlicensure training for pharmacists and training for technicians. Similar to the individual pharmacist-supervisor bearing the responsibility for the technician' s work product, the profession has a responsibility to assure that technicians are properly educated and trained to undertake the work assigned to them. Without standardization of professional training requirements for technicians, the profession is deficient in meeting its responsibility to society. The 2002 white paper is mandatory reading for anyone concerned with this issue. It clearly lays out the challenge to the profession.

■■ Impact of the ALLHAT Study Results on Managed Care
The results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) were released on December 17, 2002. Up to that time, many clinicians and managed care Pharmacy & Therapeutics (P&T) committees relied on the JNC VI (Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure) guidelines that were published in 1997. 1 Based on evidence-based studies, these guidelines strongly encouraged the use of low-cost diuretics and beta adrenergic blockers as the preferred initial therapy for most patients diagnosed with hypertension.
Though hundreds of clinical studies have been published since 1997, most had fewer patient numbers, lower-risk patients with milder forms of hypertension, and limited comparisons with other classes of pharmacological agents. The JNC has patiently waited for the results of ALLHAT before updating their national guidelines. How will the angiotensin converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs) compare to the diuretics in patient outcomes? Are the increased costs of these agents balanced by improved clinical outcomes, including lower mortality and fewer hospitalizations? Many health care dollars have awaited the decision from ALLHAT and JNC VII on which drug is preferred for hypertension.
The ALLHAT study was a practice-based, randomized clinical trial of antihypertensive pharmacologic treatment (also cholesterol treatment in a subset) in more than 40,000 high-risk patients over the age of 55 years, with a large minority representation. To be included, patients had to have stage 1 or stage 2 hypertension with at least one additional cardiovascular risk factor: history of myocardial infarction (MI) or stroke, any revascularization procedure, documented atherosclerotic heart disease, type 2 diabetes mellitus, high-density lipoprotein (HDL) < 35 mg/dL, left ventricular hypertrophy (LVH), or cigarette smoking. Notable exclusions included patients with recent MI, stroke, congestive heart failure or angina, those with ejection fractions less than 35%, and those with renal insufficiency.
The primary objective of the ALLHAT study was to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal MI differs between a diuretic (chlorthalidone) versus an angiotensin converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or an alpha adrenergic blocker (doxazosin). These agents were selected as representative of their therapeutic class. Open-label drugs (atenolol, clonidine, reserpine, hydralazine) were allowed in combination therapy in order to reach the therapeutic goal of blood pressure <140/90 mm Hg. Secondary objectives included all-cause mortality, stroke, combined CHD, combined cardiovascular disease (CVD), and others.
The objective of the lipid-lowering arm was to determine if an HMG-CoA reductase agent (pravastatin) would decrease the risk of all-cause mortality in patients with and without CHD over the age of 55 years with moderate cholesterol elevations (and hypertension) compared to "usual care" (lifestyle change). For entry into this arm of the study, patients with documented CHD had to have a baseline fasting low-density lipoprotein (LDL) in the range of 100 mg/dL to 129 mg/dL, be without coronary heart disease, and have a baseline fasting LDL in the range of 120 mg/dL to 189 mg/dL. Patients were excluded if they were prescribed a cholesterol-lowering drug.
The scope of the ALLHAT trial is unprecedented in clinical research. The study started in 1994 and included 623 clinical sites that enrolled 42,418 patients in the hypertension arm and 10,355 patients in the cholesterol arm, with an average follow-up of 5 years. More than 500,000 visits were conducted, with more than 2 million bottles of prescription medication dispensed. Subset analysis included age, gender, ethnicity, and diabetes. The study was sufficiently powered to detect very small differences in clinical outcomes.
In January 2000, the doxazosin arm of the ALLHAT study was prematurely discontinued. When compared to chlorthalidone, patients assigned to doxazosin had no difference in the risk of fatal CHD, nonfatal MI, or total mortality. 2 However, the doxazosin arm did have a higher risk of stroke and combined CVD. In particular, the CHF risk was doubled (the 4-year rates were 8.13% versus 4.45%; relative risk was 2.04; 95% confidence interval 1.79-2.32; P<.001).
The initial results of the hypertension and cholesterol arms of the ALLHAT study have now been published. [3][4] In the cholesterol arm, the baseline characteristics for the statin and usual-care group were comparable. At year 4, the statins had a greater decrease in total cholesterol (17% versus 8%) and LDL (28% versus 11%) compared to the usual-care group. The average decrease in total cholesterol for all patients (statins and usual care) in this arm of the study was 9.6% compared to 20.2% in the 8 other major lipid trials. There were no statistical differences in all-cause mortality, CHD, or incidence of cancer between the groups. At year 4, 17% of the usual-care patients were placed on a statin, which may have impacted the final results. It is also possible that improved blood pressure control may have favorably impacted the clinical outcomes. The conclusion was that both lifestyle changes and statin therapy can lower cholesterol; these results are in agreement with the current National Cholesterol Education Program' s Adult Treatment Panel III guidelines. 5 The baseline characteristics of all 3 treatment groups in the hypertension arm of the study were comparable. At 5-year follow-up, the average blood pressure in the diuretic (chlorthalidone) group was 133.9/75.4 mm Hg versus amlodipine 134.7/74.6 mm Hg versus lisinopril 135.9/75.4 mm Hg. The difference in the systolic blood pressure between chlorthalidone and lisinopril was statistically significant (P<.001) as was the difference in diastolic blood pressure between chlorthalidone and amlodipine (P<.001); the differences may not be clinically significant, however. Nearly 60% of all treatment groups required additional therapy to reach the blood pressure goal; the impact of openlabel drugs on the results is unknown at this time. In the diuretic group, 68.2% of the patients were at their blood pressure goal at year 5 of the study compared to 61.2% on lisinopril (P<.001) and 66.3% on amlodipine (P=.09). Chlorthalidone and amlodipine were better tolerated than the lisinopril. In the diuretic group, there was a slight, but statistically significant, difference in biochemical abnormalities such as total cholesterol, potassium, and incidence of new diabetes.
There were no differences in the primary outcome (fatal CHD and/or nonfatal MI) among the treatment groups. However, there was an increase in the risk of stroke in the African American patient subset in the lisinopril group compared to the diuretic group (relative risk 1.40; 95% confidence interval 1.17-1.68; P value not stated in subset analysis). There was no increase in risk of stroke in the non-African American patient subset. The diuretic group had a significantly lower incidence of heart failure compared to amlodipine (relative risk 1.38, 95% confidence interval 1.25-1.52; P<.001) and lisinopril (relative risk 1.19, 95% confidence interval 1.07-1.31; P<.001). The higher incidence of biochemical abnormalities in the diuretic group did not adversely impact any clinical outcome.
One of the practical effects of these new ALLHAT study findings is that managed care pharmacists have additional support to recommend diuretics as first-line agents for hypertension. In the past, most of us have encouraged the use of diuretics based on the results of older studies and their lower cost. Their use has been validated with additional evidence from the ALLHAT study findings that demonstrated equal or superior clinical outcomes with the diuretics compared to the highly marketed, widely prescribed, and more expensive ACEIs and CCBs. The ALLHAT study results will no doubt be challenged vigorously by the pharmaceutical industry, and further analyses of the data will be forthcoming over the next one to two years.
There is certainly a place for ACEIs, CCBs, and beta adrenergic blockers in the management of hypertension, especially in

■■ Assessing the Value of the Quality of Health Economic Studies (QHES)
Ofman and colleagues address an important challenge, that of increasing the use of economic evaluations among decision makers. 1 Specifically, the study examines whether a scoring algorithm for checklists, referred to as the Quality of Health Economic Studies (QHES), facilitates the identification of highquality economic evaluations. The use of checklists and summary scores is not new to health care, and the limitations of quality checklists have been previously identified. 2 Checklists typically cannot separate the quality of reporting from the validity of the design and conduct of a trial. Many checklists contain items that are not directly related to validity but to the precision of results (e.g., power calculations) or generalizability (e.g., inclusion and exclusion criteria). 3 When checklist items are weighted and aggregated into a summary score, such limitations can be compounded. Despite the appeal of a summary score to measure quality, research has found that the use of summary scores provides unreliable assessments of validity. 4.5 It is against this backdrop that the QHES should be consid-ered. While the objective of QHES is to discriminate the quality of studies, its theoretical basis is unclear. Many checklist items are more closely related to reporting quality or interpretation of results than internal validity (i.e., the strength of the cause-effect relationship). For example, the checklist places significant weight on issues such as transparency, whether the study objective was clearly stated, and to a lesser extent, the funding source. Important issues related to internal validity were not included in the checklist, such as the nature of randomization and blinding. For example, a cost-effectiveness study that had adequately concealed randomization and was double-blinded could receive the same score as a study that inadequately concealed randomization and had no blinding. This is problematic since both poor allocation concealment and blinding have been associated with bias. 6 Similarly, the checklist lacks questions to address the internal validity of observational economic evaluations.
The authors did attempt to validate the QHES among health economists, decision makers, and through their own work. For the health economists who were surveyed, the summary score generally correlated with a more qualitative evaluation. However, no such assessment was conducted for decision makers, who were identified as the key audience for the QHES.
Furthermore, while there was evidence of convergent validity among health economists, there was a mixed reaction to the usefulness of the instrument. The authors indicated that they found a greater acceptance for the QHES among decision makers than among health economists. However, the forum in which the data was collected, a group discussion at an annual meeting of a professional society, set the stage for possible selection bias (as evidenced by the large representation from the pharmaceutical industry), social desirability bias, and, hence, overestimation of the utility of the instrument.
The authors cite further evidence of the utility of the instrument based on its use in the review of 30 economic evaluations of GERD treatments. Yet, no evidence of validity or utility was presented since QHES results were not compared to a separate assessment and no mention was made of the time or difficulty in completing the QHES in this application, relative to other approaches. That said, higher scores on the QHES were associated with GERD studies that were published after 1996, had researchers with academic affiliations, and had been conducted in the United States. Perhaps these characteristics are proxies for higher-quality studies, but the authors never addressed this issue.
The authors propose that the QHES may be simpler for decision makers to use and that it may have equal or perhaps greater ability to discriminate study quality than other checklists. To adequately answer these questions will require rigorous research among decision makers in real-world situations. However, it should be made clear that the need for validation is not unique to the QHES checklist. Many checklists have been designed to facilitate the review of economic evaluations by decision makers, yet the ability of any of these checklists to measure what they are supposed to measure remains unclear.
Research is needed to examine which criteria for assessing the validity of cost-effectiveness studies are important determinants of study results and in what situations. For example, what is the relationship between quality scores (QHES, as an example) and treatment effect (i.e., cost-effectiveness measure)? Do lowerscoring studies tend to produce more variable estimates of costeffectiveness? Do certain components of the checklist (e.g., sufficient time horizon) relate to the size of the treatment effect? Do quality scores vary across study type (i.e., randomized controlled trial, model, and observational study)? This type of methodological work is virtually extant in the pharmacoeconomic discipline, but with the plethora of quality checklists and the substantial resources devoted to the conduct of pharmacoeconomic studies, such a strategic approach seems viable.
Meanwhile, readers of economic evaluations should be cautious not to assume a false sense of precision in the use of summary quality scores since they generally have not been supported by empirical evidence, may actually be misleading, and are potentially more time consuming.

■■ Summary Quality Scores for Pharmacoeconomic Studies: Balancing Validity With Need
Once a product has received marketing approval from the U.S. Food and Drug Administration, decisions regarding insured access to these agents are immediately raised. The existence and amount of the insured benefit for specific agents requires weighing the evidence for clinical gains and their associated costs against similar measures for competing products and therapies. Pharmacoeconomics provides a systematic, explicit, and objective basis for making and defending such drug benefit decisions. However, lack of standardization in the field 1 and the differences in perspectives, knowledge, and interests across and within the producers and consumers of pharmacoeconomics has limited its impact on drug coverage decisions. As the methodology advances, consumers of pharmacoeconomic studies require an efficient tool to identify superior studies. In this issue of the Journal, Offman et al. propose such a scoring instrument, the Quality of Health Economic Studies (QHES). 2 Beginning in 1973, clinical epidemiology has consistently identified large variations in the rates of performance of medical procedures and use of specific products. 3 As health care costs have increased, drug costs and effectiveness analyses have become common; however, the explosion of pharmacoeconomic studies has also included some of uncertain quality, rigor, or validity. Pharmacoeconomic studies have nevertheless been subject to increasing standardization. Some are still viewed with skepticism by health plans and insurers who perceive the potential latitude in permissible assumptions as resulting in less than objective evidence. However, purchasers face constant pressure to determine the relative value of marketed pharmaceuticals and to make decisions with imperfect and disparate information. Analyses to assist these determinations come from multiple sources, with attendant variations in quality, reliability, validity, and timeliness of content. Consequently, the assessment of quality and validity of specific pharmacoeconomic results is at the center of the decision process, and uncertainty here will continue to influence the impact of pharmacoeconomic studies.
The proposed QHES instrument will be a substantial contribution if it assists end-users of pharmacoeconomic studies to discriminate among the exploding body of literature 4 and efficiently identify the studies with superior merit. For producers of pharmacoeconomic studies, an accepted rating instrument could establish a clearer target-potentially encouraging higher quality and greater rigor. To achieve this level of acceptance and use, however, the QHES must demonstrate key validity characteristics.
A precondition for a valid rating instrument is that it be reliable. It must yield the same results on repeated trials. On this dimension, the qualitative nature of some of the QHES questions could mean lower reliability if the raters are not trained and their assessments not standardized. Otherwise, different observers may weigh the validity and reliability of health outcomes measures or scales differently. Without reliability, no instrument or measure can be valid.
Beyond being reliable, the QHES must rate studies on how well they actually answer the question posed by the research. Criterion validity, the closest aspect to what is commonly meant by validity, assesses the extent to which the measure being developed correlates with another, "gold standard" measure at the same time. 5 Questions of external validity, or generalizability, are at the forefront of issues confronting decision makers as users of such information. Whether the original study has a societal, patient, provider, or health plan perspective will determine the relevance of results to a specific setting or decision maker. One of the biggest challenges in evaluating pharmacoeconomic studies may be the interpretation and extension of the results to a different health care settin0g. Given the relative shortage of trained pharmacoeconomic analysts among management, clinicians, and other decision makers, such judgments often may be required of professionals who lack expertise in pharmacoeconomics. 6,7 The QHES was assessed for concurrent validity by comparison against the British Medical Journal checklist, the Canadian guidelines, and the Journal of the American Medical Association user' s guide. Further, it was assessed against the global opinion of experts ("criterion validity") and validated among economists, some decision makers, and through the authors' own work. However, the method for selecting these experts, the use of convenience sampling, may present a selection bias and limit confidence in the extent of generalizability of the results.
Acceptance of an instrument as scientifically sound requires that it represent the full content of each of the attributes being measured ("content validity"). While content validity may be relatively easy to assess in established disciplines and with established tests, content validity has proven to be exceedingly difficult to establish with evolving concepts or disciplines, such as pharmacoeconomics. The QHES addresses many of the essential domains by which the soundness of an economic analysis is assessed; however, to the extent that it omits items pertinent to observational qualitative studies, its content validity might be compromised. Such studies may involve domains that are not captured by the questions in the QHES.
The value of an applied instrument is largely determined by its construct validity, a concept more appropriate to a dynamic field such as pharmacoeconomics. Construct validity is established over time by the consistency of findings across different QHES users. Such consistency was found among the experts consulted for this study, and, to that extent, the instrument was determined to have adequate construct validity. However, results from its application have yet to be demonstrated (a) across the spectrum of decision makers from health plans, managed care providers, pharmacy benefit managers, hospital Pharmacy and Therapeutics committees, or researchers, and (b) for the range of the decisions that must be made.
In general, however, it is important to note that the concept of validity is broader than just the validity of individual aspects or measurement approaches. The QHES attempts to synthesize health economic evaluations so that they are useful in decision making and, ultimately, insurance coverage determinations as well as the development of practice guidelines. Summary scores should constitute just one component of an economic evaluation. Until a gold standard for pharmacoeconomic studies is developed, more research is needed to strengthen the link between theory and practice.
Survey research supports decision makers' ability to discern differences and to balance the overall influence of socioeconomic assessments that vary in quality, availability, timeliness, comprehensiveness, and validity. 7 Ultimately, executives and managers must make timely decisions-often with incomplete information or with information from sources from which potential conflicts of interest cannot be ruled out and must be balanced with their results. 8 Consequently, the QHES may initially be more useful as the first of a 2-stage screening process for decision makers under time pressure and with limited resources and less experienced analysts. Not surprisingly, the authors noted that the QHES had greater acceptance among decision makers than among health economists. For the former, the QHES might efficiently help identify those studies not to be included in a dossier or subjected to more rigorous assessment. A subsequent, in-depth second stage might then focus time and resources on critical examination of the remaining studies-possibly not being bound or influenced by the initial QHES score used to sort the studies initially.
To remain relevant for pharmacoeconomic studies, the QHES instrument must evolve and continue to improve in reliability and validity for a broad spectrum of decision makers. Performing pharmacoeconomic assessments is time-consuming and expensive; if the QHES can validly expedite these reviews, it may lower their initial cost and encourage more timely updates.
Just as the QHES will require refinement as experience with it accumulates, users will also need to address the minimal competencies required of those who use it and who make decisions based upon it. Even if the QHES validly predicts the quality of the studies being used by formulary decision makers, it does not, and probably should not, predict the extent to which these studies influence the decision-making process. A screening instrument such as the QHES should probably not be a replacement for expertise in pharmacoeconomics, only a supplement to it.

■■ Out of Illness, Into Life: Pain Management and the Need for Triptans
In some ways, my favorite patients are those with no insurance. The reason? They choose reasonably. They choose the way America says it wants us to choose, in a cost-reasonable way that insured patients often feel little inclination to choose.
Would one of my uninsured patients choose to take triptans several times a week? Not a chance. The costs would clearly be too high. My uninsured patient would be more likely happy with amitriptyline-preventing the headaches, for pennies a day. Of course, we would discuss the possibility of weight gain. But we'd handle that, possibly by a healthier hypoglycemic diet.
My uninsured patient might not see me for months. The headaches that break through would be handled with over-thecounter drugs, occasional pain pills, or maybe that rare triptan if the "miseries" had really set in. The rest of the time the illness would be handled by prevention-combined with a healthy dose of reasonable expectations. Now, my headache colleagues might be saying "but these aren't my patients, the ones with the really miserable migraines, the ones who feel miserable every day." Actually, they are. They have the same biology. They just don't have the same way of behaving with that biology.
My uninsured patients don't have easy lives. Many of them have fallen on quite hard times. They have the miseries. A lot of them just don't discuss their anguish via their headaches. They have pain, but they don't discuss it via "the pain." And, part of the reason they don't do this is because they can't afford to manage the pain by taking all of this expensive medication to chase after it. They have migraine. They fulfill all the International Headache Society criteria. They just don't find it practical to translate the pain of their life anguish into the pain called migraine. And so the migraine disease doesn't become the way of being.
Consider, in this regard, and for comparison, one of my favorite insured patients. She is a very nice young woman I've treated for years. She has migraine, and she has had "bad migraine" (whatever we may conceive of this to be in biological terms). In the last couple of years, she has had a very difficult time. Her headaches were very frequent and very difficult to treat in spite of all the best management strategies. She had her therapeutic layer of preventative mediations, her therapeutic layer of healthy lifestyle (diet, exercise, sleep, etc.), her therapeutic layer of trigger-factor controls (hormones, stress, foods, etc.), her therapeutic layer of ancillary techniques (biofeedback, acupuncture, chiropractic, etc.), her therapeutic layer of limited (nonrebound) analgesics, and, of course, her therapeutic layer of limited (nonrebound) abortives, including the triptans. Yet, she was doing poorly. Headaches were frequent. She was unhappy.
Actually, I should turn that around: she was unhappy, headaches were frequent. She and her husband had been struggling for a long time. And, finally, she decided that in spite of her "being alone" fears, her 3 children, financial worries, and the rest, it was time for the two of them to go in different directions. She pursued divorce.
It was difficult. But, there is a point to our story. She saw me recently-about 8 months into the divorce-and, beaming, she told me that she has not had a bad headache since her husband moved out. She still has the migraine illness. But, the illness is now vastly easier to control. Mostly, we are treating her anxiety at this point.
Here is another experience to ponder. While recently at some neurological meetings, I took the opportunity, as I often do, to inquire of colleagues about how common illnesses are managed in other countries. I think this helps me to determine what is "necessary" and what is cultural. One of my colleagues at this meeting was from India. And, it so happens his mother had migraines. She lives in rural India. And, she has no insurance. So I asked, "What does your mother do to treat her headaches?" His answer: "When she gets them, she lays down for about half an hour." Apparently this is her major form of treatment. Of course, this is "N=1." This is anecdotal. And, in a rural setting, it might be more practical to lie down for half an hour. Yet, this is a worthwhile piece of information. This is inexpensive treatment, and she feels it is acceptable.
And, here is one more story. I was recently reading the report of another neurologist in which he described one of his patients who was on a great deal of medication for migraines. She was in his office complaining of severe migraine. He was evaluating what to do next. He reported that on her analog pain scale, she reported pain being 9 out of 10 (10 being the score of "the worst pain imaginable"). So, by her appraisal, she was very close to the most extreme end of the scale. Yet, interestingly, on his exam, he observed her to be "a woman in no apparent distress," and he didn't seem bothered by the disparity.
It is actually rather common to see patients who report having severe headaches-including at the moment of evaluation-while physical examination reveals the patient appearing normal, or even cheerful. This disparity is so common that it often no longer even generates recognition. Yet, isn't it revealing? Intriguingly, in my patients with no insurance, this is rather rare. If they have a bad migraine, they look ill.
The notion of "bad migraine" is complex. For a few patients, it is the presentation of visible misery. During a bad migraine, the patient may appear pale, diaphoretic, obviously nauseated, and withdrawn into wincing pain. Yet, it is quite routine to see patients who report having "bad migraine" illness where this is never really observed. Instead, the patient presents to the office with major report of pain but, often, remarkably little evidence of pain (although perhaps the haggard appearance of chronic stress). When the literature talks about "bad migraine," it does not talk about patients who are measured to have bad physiology (analogous to a patient with bad cancer who has metastases everywhere, or a cardiac patient with bad heart disease who has ankles the size of calves). Rather, literature discussions of "bad migraine" tend to proceed based on patient claims of pain, often "measured" via instruments such as a visual analog scale, that really only succeed in documenting a claim. Therefore, discussions of "bad migraine" need to be recognized as not the scientific equivalent of many of our other discussions of severe disease. So, with these 3 stories, we may then return to the perception of "need" for triptans. As in other realms of life, perception is a critical aspect of perceived need. My uninsured patients do not perceive that they need great quantities of these expensive medications. On the other hand, my insured patients may feel that they do. So, what part of this "need" is biology, and what part is sociology?
Even in my own patients that I have revealed above, the issues are not simple. I knew my young female patient with refractory headaches was suffering anguish as much as migraine. But, I also knew that she was not willing to "go there." So, I managed the illness as well as I could under biological approaches while still discussing with her that high-grade stress was actually the cause of her refractory state (later confirmed). When she was ready, she could obtain more effective solutions.
The management of pain, whether under the auspices of migraine or some other mechanism, is complex. Unlike congestive heart failure, renal failure, or a host of other clearly structural problems, the management of pain is a management of mixed issues: partly biology, partly psychology, and partly sociology. Physicians may choose to ignore the latter 2 factors because of the convenience of doing so. However, high cost and excessive service will be the result. And, in the final analysis, the patient' s quality of life will deteriorate.
In this issue of the Journal, Adelman and Belsey examine the relative cost-effectiveness of triptans. The erudite work by the authors adds to our perspective of choices within the class. But, possibly, it makes a subtle yet critical transition that is problematical. The initial portions of the article address quite well the cost considerations between drugs. However, the latter portion of the article presumes that freer use of triptans may reduce costs overall by reducing emergency room visits. However, as a headache specialist, it is my opinion that the best way to reduce ER visits is to prevent the headaches. And, triptans are not effective in that regard. If patients excessively chase after the headaches, they tend to beget more of the same-chasing after the headaches. This is not ultimately the route to reducing costs. So, the class of drugs is certainly excellent. And, the authors help us choose among the class for appropriate use. However, in my opinion, freer use of abortives may only abort, and not control.

■■ Medicare PPOs and Managed Care
It appears to be a good time to review some of the fundamental principles of managed care. A recent caption read "PPOs will halt the slide in Medicare managed care." 1 More than 15 years ago, managed care was defined by core principles that included negotiated, provider reimbursement rates through preferred provider organizations (PPOs) 2,3 risk-contracting between health plans and providers, 4 and increased accountability from determination of medical necessity and appropriateness through operation of utilization management programs. 5 By the end of the 1980s, managed care was defined by at least one of 10 fundamental components that included prospective pricing, usual, customary and reasonable price determinations, service bundling, peer review, mandatory use review, benefit redesign, capitation payments, channeling, quality criteria, or health promotion. 6 The Medicare PPO demonstration program that began January 1, 2003, modified, but did not change, the managed care features of the Medicare+Choice program. In fact, the Medicare+Choice PPO option in 2003 is not new at all. PPOs have been eligible to participate in Medicare+Choice since its inception, but only 2 PPOs had participated in Medicare+ Choice prior to the program change in 2003 that pays participating PPOs the greater of the county-specific premium amount or 99% of the national per-patient average annual payment amount in fee-for-service Medicare. The media attention to the Medicare+Choice PPO option may overstate the potential since, ironically, anti-trust enforcement from the federal government makes it difficult for physicians and other providers to form collective units to contract with Medicare PPO sponsors. Nevertheless, Medicare+Choice was not abandoning managed care in 2003 but, in fact, retained all of the former features of Medicare+Choice and all of the features that were first used to describe managed care 15 years ago. For Medicare members, the "new" feature in Medicare+Choice in 2003 allowed the use of providers outside the designated network, but at a higher out-of-pocket cost. In this way, Medicare+Choice resembles most employer-sponsored health plans that had years earlier adopted tiered, point-of-care, cost-share features to permit beneficiaries more choices in providers and services.

■■ Burden of Prescription Drug Costs in the United States
What is the true "burden" of prescription drug costs in the United States? Talk to a cab driver without insurance, and prescription drug costs are expensive and even unaffordable. Talk to the person who builds the cab, and prescription costs in the United States are not a problem. One person pays $3 or more per day to lower serum cholesterol, and the other pays less than 10 cents per day for the same drug.
The cab driver pays for the entire cost of the prescription drug at the point of service. The union worker who builds the taxi cab pays a fraction of the cost of the prescription drug at point of service, often less than 10 percent of a negotiated, contract price of the drug. This copayment arrangement for the insured, union worker reduces the personal burden of prescription drug costs and can "insulate" the worker from true prescription drug costs.
The burden of prescription drug costs can be more acute for the elderly, who on average use 3 times the number of prescriptions per month compared to persons younger than 65 years. 7 Yet, a remarkable 17% of Medicare beneficiaries had no ($0) spending on prescription drugs in CY 2001. 8 Spending of $1,000 or more was found among 28% of Medicare beneficiaries and accounted for 76% of total expenditures for prescription drugs for this population.
Survey data from 10,927 nonstitutionalized seniors in 8 geographically diverse states in 2001 showed that 35% of seniors had drug coverage under a Medigap policy, 25% of seniors were enrolled in state pharmacy assistance programs, and 19% of seniors in Medicare health maintenance organizations (HMOs) spent at least $100 per month ($1,200 per year) on prescriptions in 2001. 9 Medicare HMOs were important sources of drug coverage for seniors in California (30%) and Colorado (24%) but were less important in other states, ranging from a low of 7% in Illinois to 14% in Pennsylvania. Unfortunately, Medicare+Choice plans became unavailable to about one third of all Medicare+Choice members, about 2.5 million people, between 1998 and 2002, 10  In a previous issue of the Journal, Cox and Henderson found that Medicare+Choice members with an annual drug benefit maximum (dollar limit) relied on prescription drug samples to mitigate the financial burden of prescription drug needs. 12 This finding highlighted the controversy surrounding this potentially self-defeating behavior since drug samples in physician offices are generally higher-cost drugs without generic equivalents. The use of drug samples might contribute to complacency among some physicians rather than encouraging them to select lower-cost therapeutic alternatives for these patients that would truly reduce the financial burden of prescription drugs for the elderly. In this issue of the Journal, McKercher, Taylor, Lee, Chao, and Kumar found that prescription drugs in elderly families accounted for approximately twice the proportion of total out-of-pocket medical care burden compared to nonelderly families, 45.6% versus 23.7%, respectively. The higher proportion of total medical care burden and total economic burden attributable to prescription drugs in the elderly was traced to larger prescription quantities, price, and utilization but not more expensive drugs. 13 This finding may be explained, in part, by the higher proportion of total prescription drug spending attributable to generic drugs, 20.5% for the elderly families versus 18.7% for nonelderly families. Access to data on days of therapy, in addition to prescription (Rx) counts and dosage units, would have helped to further clarify this finding. 14 The economic burden of prescription drugs for nonelderly and elderly families will increase, at least in the short term. Prescription drug spending is projected to grow by at least 13% and as much as 20% in 2003. [15][16][17] An upward spiral of economic burden is created by rising prescription drug prices and prescription drug utilization coincident with stagnant personal income. The perceived burden of prescription drug expenditures also will increase with declining household wealth in the United States, which fell in the third quarter of 2002 to its lowest level since 1995. 18 The burden for elderly families is not distributed evenly, and prescription drug coverage is associated with higher utilization for elderly persons with ostensibly the same health status. For elderly persons with no chronic disease conditions, drug utilization is more than 2 times (112%) higher for persons with prescription drug coverage than for persons without prescription coverage. The difference in drug utilization for the elderly with and without prescription drug coverage declines steadily with declining health status. For the elderly with 5 or more chronic disease conditions, the difference in prescription drug utilization is just 15%, 3.7 prescriptions per person per month for the elderly with prescription drug coverage versus 3.2 prescriptions per person per month for the elderly without prescription drug coverage. 19 About 76% of Medicare beneficiaries had prescription drug coverage at some point in 1999. 20

■■ Preventing Medication Errors and Adverse Drug Events
The House Energy and Commerce Committee on September 25, 2002, approved a bill to create a confidential, voluntary database that health care providers could use to report medical errors. 21 The legislation would have to be reconciled with a similar bill approved the previous week by the House Ways and Means Committee and a Senate bill, the Patient Safety and Quality Improvement Act. 22 The House Energy and Commerce Committee bill would allow patient-safety organizations to monitor the database and use the information to develop recommendations on ways to prevent future mistakes. 23 The legislative proposal received fuel from a government research report that estimated medical errors cause thousands of deaths and injuries and cost $29 billion a year.
Yet, there is disagreement about the scope and severity of the threat to patient safety posed by the U.S. health care system. The first Institute of Medicine report on the matter, To Err Is Human, was released in late 1999 and set off a firestorm of debate about the estimated versus true magnitude of the threat to patient safety in the current U.S. health care system. 24 This IOM report was criticized for overestimating the incidence of preventable deaths due to medical errors and for adding to the miscommunication on the subject by fostering the interchangeable use of "medical error" and "adverse event." [25][26][27] A recent study of physicians and nonphysicians of their first-hand experiences with medical errors helped to provide additional perspective on the perceived severity of the threat to patient safety. Parallel surveys of 831 physicians and 1,207 nonphysicians (adults age 18 or older) conducted between April 11 and June 11, 2002, found that 35% of physicians and 42% of the public reported personal experience with medical errors in their own or a family member' s care. However, neither group viewed medical errors as one of the most important problems in health care in 2002. 28 These findings may call into question the sense of urgency to stamp out medical errors expressed by many observers, consultants, and national organizations. The findings of these surveys also appear to add support to those who disagree with the reports of widespread medical errors in the U.S. health care system 29 and to those critical of patchwork methods to improve health system quality. 30 Reliable measures are necessary to benchmark and assess the value and return on investment from allocation of finite resources to eliminate errors of commission in health care. Some argue that finite resources might be better spent to reduce errors of omission, such as the failure to control hypertension. 31 While the debate continues regarding the true magnitude of the threat to patient safety posed by the U.S. health care system, evidence is accumulating regarding the disparity between estimates of medical errors and the actual incidence of medical errors and harm. Fundamental to our understanding is the recognition that a medical error (ME) may or may not be associated with an adverse event (AE). 32 Similarly, a medication error may result in no harm and no adverse drug event (ADE). 33 The U.S. Pharmacopeia Center for the Advancement of Patient Safety reported in December 2002 that data reported by 368 health care facilities in 2001 showed 2.4% of hospital medication errors to have resulted in patient injury or death; the incidence of death from medication error was 14, or 1.3 per 10,000 medication errors. 34 A study published in September 2002 based upon direct observation, a method more reliable than other methods, found a 19% error rate in medications (drug MEs) and a 7% rate of potentially harmful drug errors (ADEs). 35 Certainly, the first priority is to prevent the ADEs and adverse medical events (AMEs) with the worst outcomes, death or disability. Categorization and differentiation of medical errors and medication errors from ADEs and AMEs and stratification of the events by level of severity of harm 36 will permit the focus necessary to allocate the resources to prevent them. It is now well accepted that the preferred method to improve identification and prevention of errors and adverse outcomes from errors involves self-investigation of system causes rather than external review and punishment of organizations and individuals. [37][38] The method of error reporting is also critical to the identification of true-positive incidences of medical errors, including medication errors. Self-reporting of medication errors may under-report the true incidence by as much as 95%, 39 and current methods of collecting information on ADEs may under-report the true incidence by as much as 99%. 40 In this issue of the Journal, Grissinger, Globus, and Fricker, from the Institute of Safe Medication Practices (ISMP), focus on the patient-practitioner interaction as a primary opportunity to reduce medication errors. 41 This is also the principal focus of a campaign launched by the U.S. Food and Drug Administration (FDA) in August 2002 that had the theme: "Think through the risks and benefits of medicines." 42 This consumer-oriented education campaign urged patients to ask questions of their physicians and pharmacists and to become more active in the process of assessing the benefits and risk of prescription drugs: "before using any medicine-as with many things that you do every day-you should think through the benefits and the risks in order to make the best choice for you." Managed care pharmacy can effectively use the same metaphor: when driving a car, you wear your seat belt; when taking medications, you talk to your pharmacist and physician.
Managed care pharmacy can also have a measurable effect on the medication errors and ADEs through reliance on the principles of continuous quality improvement, a fundamental, core area of the Academy of Managed Care Pharmacy' s "Pharmacy' s Framework for Drug Therapy Management in the 21st Century." The framework' s self-assessment tool contains specific tasks and components within key functional areas that permit individual, organization, and system analysis of opportunities for quality improvement in drug therapy management. Key functional areas in patient safety and reduction of medication errors and ADEs are interspersed throughout the framework, with emphasis on patient-practitioner interaction in interpersonal communication (area 1.1), patient education (1.3, 4.4, 5.3, and 6.3), patient and worker safety (1.4), drug selection (3.2), coordination of care (3.5), etc. 43 Many of the solutions necessary to prevent and reduce medical errors and medication errors will involve changes in processes and systems that "make it easy to do it right." 44

■■ Quality of Health Economic Studies (QHES)-Tool or Mask?
Managed care pharmacists face a mountain of data when making decisions about the relative value of alternate drug therapies in individual patients and in the selection of preferred agents in prescription drug formularies. The objective is to apply rules of evidence-based medicine to derive the information that will be important to develop and refine clinical practice guidelines (CPGs) and clinical practice models (CPMs) that will make it possible to achieve effective disease management. This paradigm might be made more clear by thinking of this continuum in terms of structure, process, and outcome in which the "structure" derives from evidence-based medicine, the "process" from application of CPGs and CPMs, and the outcome as successful attainment of disease management.
The U.S. National Library of Medicine reported an average 10,000 new lines (articles) referenced in MEDLINE each week at year-end 2001. 45 The amount of data and information in the medical literature is growing further and is now quite easily overwhelming, setting aside the additional data and information disseminated in the lay press and on the Internet. It is now more important than ever to find tools to help filter and interpret enormous amounts of data and thousands of medical literature references. The Quality of Health Economics (QHES) instrument may be such a tool. On the other hand, this tool, as any tool, can be misapplied. In addition to possible inherent flaws in the instrument, some of which will only be discovered upon repeated use and scrutiny of the results, users of the QHES have the potential to distort the findings of the studies that they are measuring.
Ofman, Sullivan, Neumann, et al. in this issue of the Journal, take the bold step of introducing a new instrument, the QHES. 46 The true value of this instrument and method will not be determined immediately, and readers have reason to be critical. Shaya and Lyles in an accompanying editorial suggest that managed care pharmacy should evaluate critically this new instrument and method. 47 Motheral argues for caution and even rejection of the instrument and method. 48 Science advances through scholarly debate. By articulating and applying the QHES, Ofman et al. permit others to critique the instrument and method and to propose changes that will enhance value by increasing its validity, reliability, and usefulness. We are certainly in need of better tools to evaluate published data.
The QHES has value, perhaps not so much for its final numeric "score," but in its qualitative analysis of the results of assessment of individual items in the 16-item instrument. Some researchers will no doubt want to change the weight of individual items to improve the utility of the QHES in application to particular uses. The architects of the QHES will need to explain for other researchers that the 3 compound items (numbers 5, 8 and 11) in the QHES require affirmation of both questions. Item number 5, "Was uncertainty handled by: 1) statistical analysis to address random events; 2) sensitivity analysis to cover a range of assumptions?" could have one "yes" and one "no" answer, yet the weight for the item is "9." Item number 8 asks 2 questions and has a weight of "7": "Did the analytic horizon allow time for all relevant and important outcomes?" "Were benefits and costs that went beyond 1 year discounted (3% to 5%) and justification given for the discount rate?" Item no. 11 also has 2 questions, with one score of "7": "Were the health outcome measures/scales valid and reliable? If previously tested valid and reliable measures were not available, was justification given for the measures/scales used?" At the least, the QHES instrument and method present us with a useful platform for scholarly debate on attempts to bring more science to pharmacoeconomics, a relatively young discipline still in search of credibility in the scientific community.

■■ Antihypertensive Drug Effects on Renal Function and Myocardial Infarction and Implications of the ALLHAT Study Results
In managed care we must study the effects of drugs outside the realm of randomized clinical trials (RCTs) to ascertain their real value in uncontrolled, real-world settings. This is particularly true in the ubiquitous treatment of hypertension. One area of particular interest is in the growing body of evidence that some drugs have renal protective effects in excess of their hemodynamic effects in blood pressure reduction. A randomized trial involving 1,094 African Americans aged 18 to 70 years followed for a minimum period of 3 years and up to 6.4 years found that ramipril, an angiotensin converting enzyme inhibitor (ACEI), in a dose range of 2.5 mg up to 10 mg per day, appeared to be more effective than beta-blockers (metoprolol dosed between 50 mg and 200 mg per day) or dihydropyridine calcium channel blockers (amlodipine dosed between 5 mg and 10 mg per day) in slowing the decline in glomerular filtration rate (GFR), an important indicator of kidney function. 49 The ACEI was associated with risk reduction of 22% in the composite outcome (reduction in GFR by 50% or more [or greater than or equal to 5 mL/min per 1.73 m 2 ]) from baseline, endstage renal disease or death), compared to metoprolol or amlodipine; there was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups; and there was no apparent additional benefit in slowing progression of hypertensive nephrosclerosis associated with a lower blood pressure goal of 92 mm Hg or less, compared to the usual blood pressure goal of 102 mm Hg to 107 mm Hg.
Nephropathy, defined as proteinuria greater than 300 mg in 24 hours, will develop in 35% of patients with type 1 diabetes, usually manifested first as persistent microalbuminuria that appears 5 to 10 years after the onset of diabetes. Nephropathy will progress to end-stage renal failure. Drug therapy that lowers blood pressure and protects diabetics from development of nephropathy is obviously important in reducing morbidity and mortality. Ten years ago, captopril 25 mg 3 times a day was found to reduce by 50% the risk of the combined endpoint of death, dialysis, and transplantation compared to placebo in patients with type 1 diabetes. 50 Since then, lisinopril dosed at 10 mg to 20 mg per day was found to significantly reduce albumin excretion and microalbuminuria in normotensive type 1 diabetics, 51 thereby demonstrating the utility of ACEIs in the prevention of diabetic nephropathy as well as in its treatment. Meta-regression analysis has shown that ACEIs can decrease proteinuria and preserve GFR in patients with diabetes mellitus. 52 The MICRO-HOPE trial of more than 3,500 diabetic patients from the HOPE trial (97% of whom had type 2 diabetes) showed a 24% reduction in risk of nephropathy in an average 4.5 years of follow-up in patients who received the ACEI, ramipril. 53 There was a significantly lower albumin-creatinine ratio in the ramipril group, and these effects were greater than could be attributed to reduction in blood pressure alone.
The dihydropyridine (DHP) calcium channel blockers (CCBs) have not been shown to have comparable effects in protection from nephropathy in either diabetic or non-diabetic patients. In the Irbesartan Diabetes Nephropathy Trial, the DHP CCB, amlodipine, at 10 mg per day appeared to fare worse than placebo in the composite endpoint of time to doubling of baseline serum creatinine, development of ESRD or death from any cause, in type 2 diabetics with hypertension. 54 The effects of CCBs on risk of MI in patients with or without diabetes warrant further study. While short-acting and intermediate-acting DHPs may be associated with an increased risk of myocardial infarction (MI) 55-56 this relationship has not been found with the long-acting DHPs, 57 but experts have requested caution in the use of CCBs in treating hypertension, 58 particularly in diabetics. 59 The researchers at Wake Forest University School of Medicine who found in 1995 that short-acting calcium channel blockers may cause more harm than benefit, presented at the European Society of Cardiology in Amsterdam in August 2000 the results of a meta-analysis of 9 RCTs that compared outcomes of the use of calcium channel blockers versus diuretics, ACE inhibitors or beta-blockers for hypertension. 60 The pooled data showed a 27% higher risk of heart attack and a 26% higher risk of heart failure in patients on calcium channel blockers versus alternative therapies for hypertension: diuretics, ACEIs, or beta-blockers. 61 Overall survival was not significantly different among the alternative therapies.
Anderson, Alabi, Kelly, Diseker, and Roblin, in this issue of the Journal, failed to find a higher risk of MI in high-risk diabetic patients prescribed a combination antihypertensive drug regimen that included a DHP CCB or a nondihydropyridine CCB. 62 The well-conceived study design was undermined by a small sample size and missing data for variables such as ethnicity, smoking status, vital signs, and laboratory tests. Nevertheless, this research is useful in articulating a study design that may be used by others in managed care pharmacy to examine retrospective databases to ferret out the relationships of combination drug therapies in the development of adverse myocardial and renal outcomes in high-risk patients. Future research should also address the important question regarding dose-related effects of CCBs in combination with ACEIs or diuretics.
The impetus to perform more clinical studies of the relative value of ACEIs and CCBs in the treatment of hypertension increased in light of the results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALL-HAT), released in December 2002. It is hard to overstate the importance and potential impact of the results of the ALLHAT study. These results suggest that most of the more than 40 million Americans with hypertension 63 could be treated more effectively and more safely with low-cost diuretics such as chlorthalidone and hydrochlorothiazide, at a fraction of the cost of ACEIs such as ramipril or quinapril and CCBs such as amlodipine, felodipine and long-acting nifedipine and diltiazem. 64 The 8-year study, with a mean follow-up of 4.9 years, produced unequivocal evidence that amlodipine and lisinopril were associated with the same incidence of the primary outcome of combined fatal coronary heart disease or nonfatal MI as chlorthalidone; all-cause mortality was also the same among the three treatment groups. However, chlorthalidone was superior to amlodipine in the 6-year rate of heart failure (HF), 7.7% vs. 10.2%, relative risk 1.38, and chlorthalidone was superior to lisinopril in the 6-year rates of combined cardiovascular disease, 30.9% versus 33.3%, RR 1.10, stroke (5.6% versus 6.3%, RR 1.15) and HF (8.7% versus 7.7%, RR 1.19). Robert Anderson, one of the ALLHAT investigators, has additional observations regarding the ALLHAT study findings in this issue of the Journal. 65

■■ Prior Authorization to Manage Drug Utilization and Costs
In 1998, state Medicaid programs were responding in various ways to double-digit increases in prescription drug benefit costs. In some states such as Massachusetts, the cost increases threatened to push drug benefit costs ahead of the costs of hospital acute care services by the year 2003. Massachusetts Medicaid planned to implement "more aggressive utilization practices," Kentucky required prescribers to use lower-cost first-generation antihistamines and Florida used prescriber profiling, focusing on the use of "fourth-generation" antibiotics for upper respiratory infection in adults. 66 Florida also planned "provider education forums" to focus on drug prices. Drug formularies were not an option since state Medicaid programs have essentially open formularies because nearly all drug manufacturers pay rebates to obtain formulary status, leaving only prior authorization (PA) programs to discourage use of certain high-cost drugs. Medicaid rebates for single source and innovator multiple-source brand drugs in 1998 was the greater of 15.1% of average manufacturer price or AMP less best price. For noninnovator drugs, the rebate was 11%.
By 1999 and 2000, state Medicaid officials began to complain more openly about requirement of state programs to operate open drug formularies as part of the OBRA 1990 statute on mandatory drug manufacturer rebates. Oklahoma Health Care Authority CEO, Michael Fogarty, testified at a 29 March 2000 Senate Finance Committee hearing that two factors in the Medicaid "best price" approach contributed to the "evaporation" of savings: (a) open formularies, and (b) price adjustments by manufacturers to compensate for the mandatory rebates. 67 Fogarty recommended that state Medicaid programs be permitted to institute closed formularies to make drug manufacturers compete with lower prices.
OBRA 1993 amended the OBRA 1990 language and no longer required state Medicaid programs to reimburse for new drugs approved by the FDA, for the first 6 months after introduction. However, federal law and regulations prohibit states from denying access to drugs by Medicaid recipients, and 43 states and the District of Columbia had PA programs in place in 1996 to limit the use of nonformulary and nonpreferred drugs. 68 States have reported limited success with PA programs, and New York adopted a mandatory generic drug substitution program in November 2002 in which brand-name drugs with a generic equivalent would require a PA to be covered by the Medicaid program. The PA program could be utilized by physi-cians using voice recognition or a keypad and required the physicians to answer a "brief set of questions about why the patient required the brand product." For a multiple-source brand product to be dispensed, the prescription must include the PA number obtained by the physician, and must indicate "DAW" (dispense as written) and "brand (medically) necessary." 69 New York hoped to push its generic substitution rate to 95% from 88% of multiple-source brand drug prescriptions with the mandatory generic/PA program, a modest goal for managed care organizations working in the private employer sector.
The absence of reliable data on the cost-effectiveness of prescription drug benefit prior PA programs was highlighted in a previous issue of the Journal. 70 Any reasonable assessment of the cost-effectiveness of PA programs in prescription drug benefits would include consideration of the potential, and predictable, adverse service outcomes, including physician, pharmacy, and beneficiary, satisfaction as well as wait time and additional service costs. Such considerations in the public arena appear to be outweighed by budget concerns. Beginning with the Florida PA program for nonpreferred drugs that was launched in July 2001, several other states implemented similar programs by mid-2002. 71 The principal feature of all of these state Medicaid PA programs, including Michigan, Illinois, Louisiana, and North Carolina, was to extract additional rebates from pharmaceutical manufacturers to bring their drugs down to the "reference price" within therapeutic classes. Failure to match the reference price through supplemental rebates subjects the drug to PA. Cox-2 drugs were the first of 2 drug classes implemented in the Louisiana Medicaid preferred drug program in June 2002.
In this issue of the Journal, LaPensee describes the experience of a drug PA program in a Medicaid managed care organization (MCO) in the northeast in early 2002. 72 While Medicaid HMOs operate under a different set of rules than private MCOs and have fewer tools to manage drug benefit costs, particularly the absence of tier-copay benefit designs, the description of this Medicaid PA program has some useful information for all managed care observers. Nearly 4 out of 5 PA requests were for formulary drugs. Second, the PA rejection rate was low: only 4.4% of the more than 22,000 PA requests received each month were denied. Clearly, this is a large administrative burden, nearly 1,000 PA requests per day, of which an average of 44 were denied. The 93% acceptance rate for PAs for nonformulary drugs compares with an acceptance rate of about 75% for drug benefit PAs for commercial health plans in 1999 and 2000. [73][74]

■■ HIPAA Effects on Health Research and PBM Functions in Drug Utilization Review
The Health Insurance Portability and Accountability Act (HIPAA) of 1996 was crafted originally with the intent to better protect health insurance coverage for employees and their families when employees changed employers; i.e., to ensure portability of health insurance. 75 By the time the legislative process was complete, HIPAA had 2 primary impacts beyond portabil-ity of health insurance benefits: the standardization of medical claim information and patient privacy. For patient privacy, the original Clinton administration rules released in late 2000 were so onerous as to threaten the quality of patient care by making important patient information unavailable to the health care provider at the point of care. The proposed policy was ironic since the lack of sufficient patient information at the point of care is a major and under-recognized source of medical errors.
HIPAA implementation rules for privacy of health information released in December 2000 ultimately culminated in the "final rule" on August 14, 2002, that specified 9 elements for the disclosure authorization form for all research. 76 The December 2000 proposed rule required time-limited authorization forms for "research involving treatment" or access to existing medical records. The August 2002 version required a single form for all research, required no expiration date but specified 9 elements, including (a) proposed use and (b) amount of disclosure. The 2002 rule also permits providers to share a "limited data set" for research. As with the earlier proposed rules, the final rule on medical privacy exempts only information that has been "de-identified." Despite the relaxation of most aspects of the proposed rules, the August 2002 rules did not go far enough to relax the imminent stranglehold on communication of information necessary for optimum medical care and for adequate health care research. 77 For pharmacy benefit managers (PBMs), the effects of HIPAA are mostly additional administrative costs in policy, procedures and training. There is much to complain about in the HIPAA regulations for health plans and employers (covered entities) and for contractors to health plans and employers ("business associates") such as PBMs. There are additional administrative costs, which ultimately have to be passed along to customers, i.e., employers including public (taxpayers) as well as private employers. Yet, there is some "good" in the effects of HIPAA.
Part of the favorable aspects of HIPAA and the attention to privacy of protected health information (PHI) is more careful use of private information. Many people who previously had, and some who still have, access to certain PHI should not have had access to this personal information and will not have access in the future. It was common for the human resources manager or staff person in the HR department or finance office to receive, routinely, drug claim detail including patient name, drug name, and date of service.
Today, most PBMs have taken 2 courses of action to protect PHI while permitting officers of employers and health plans to fulfill their fiduciary responsibilities. First, drug claim detail is shared with third-party administrators, employers, and other agents with fiduciary responsibility, with the patient ID and name stripped from this claim detail; i.e., the drug claim detail is de-identified. Drug claim databases shared with the clients of PBMs typically employ scrambled patient ID numbers (deidentified). These scrambled patient ID numbers are unique and can be traced by the PBM back to the patient in cases where patient safety may be threatened, such as in a market recall of a drug. (This ability to unscramble the beneficiary identifier is not an insignificant matter since many physicians and medical practices, even today, are not able to identify active patients who have been prescribed a particular drug without searching individual medical records, one at a time.) Second, most PBMs now produce aggregate financial information, with identification of the beneficiaries, such as the list of high-cost claimants with the summary financial fields, but without identification of drugs by name. These and other business practices of PBMs protect PHI while allowing health plan sponsors and their agents to fulfill their fiduciary responsibilities.
Prior to these changes in PBM privacy policies, the human resources manager at a physician medical group, for example, would have received the drug claim detail that showed that one of its internal medicine physicians was prescribing narcotics routinely, allegedly for his spouse. Today, the PBM would investigate the matter and perhaps caution the physician about routine prescribing for immediate family members. 78 The situation was more than it appeared since the physician was suspected by the dispensing pharmacist of prescribing the narcotics for his own use. The medical director for the medical groupemployer and the PBM worked together, with the medical director blinded to the identity of the beneficiary-physician, to monitor the narcotic prescriptions from this physician for his family use. Prior to these revised PBM privacy policies, the physician could have had a reasonable charge of discrimination if any employment action had been taken against the physicianemployee. In other words, the privacy policy of the PBM protected the PHI from disclosure to the medical director or other officer of the employer (medical group).
The unfavorable aspects of proposed HIPAA regulations and some state patient privacy rules include conflicts with efforts by health care professionals to and improve the quality of care. Some physicians and patients wave "privacy" flags in order to protect profitable conspiracies in drug diversion or drug misuse by shielding themselves from scrutiny in utilization review (UR) performed by health plans and by business associates on behalf of plan sponsors. Think this happens infrequently? Ask any utilization management coordinator who deals daily with exceptional prescription drug use. The list is long. For example, patients who pay physicians to prescribe tens of thousands of dollars of sustained-release oxycodone, with street-value of hundreds of thousands of dollars. Any drug that has high value in everyday commerce, monetary or otherwise, may be associated with "theft" from a drug plan through prescriptions that are not medically necessary. HIPAA and the public attention to privacy of medical records sometimes makes more difficult the job of attaining coordination of care through utilization management (UM) interventions.
Also in the unfavorable portion of the spectrum of HIPAA privacy rules is the plethora of lawyers and consultants who talk jargon that borders on gibberish, selling compliance advice and assessment tools. HIPAA appears to be creating some new arcane rules on record-keeping, contracting, and other ministerial functions that may add to cost without necessarily adding anything to patient privacy or its protection. One health law attorney coined this phrase, "HIPAA, the death of common sense." 79 As a technical matter, the HIPAA (1996) standards for electronic transmission of health care information were delayed for one year, until October 16, 2003, by the Administrative Simplification Compliance Act (P.L. 107-105). However, covered entities (e.g., group health plans and health insurers, health care clearinghouses) and their business associates (e.g., PBMs) were required to submit a compliance extension plan to the Department of Health and Human Services (HHS) by October 16, 2002, to receive an extension. Ironically, the form for this purpose was available at the Centers for Medicare and Medicaid Services Web site 80 but could not be submitted electronically to CMS. The form had to be printed, completed, and mailed to CMS.
The final regulations for protection of PHI were effective April 14, 2001, but compliance was not required until 14 April 2003 (except for small group plans, which have until April 14, 2004, to be compliant). Proposed changes released by HHS since the December 2000 publication of the "final rules" have eased some of the onerous restrictions but do not yet make the job of UM coordinators any easier. Specifically, the patient' s advance written permission is not required for most treatment, payment, or other health care transactions. However, covered entities do not escape the requirement to (a) notify patients of their medical privacy rights, (b) notify patients of the policy and procedures employed by the covered entity to protect PHI, and (c) obtain the signatures of patients acknowledging receipt of this notification. Second, among the changes particularly relevant to prescription drug benefit management, disease management programs have a limited exception to permit covered entities to discuss treatment options and share PHI for the purpose of conducting disease management interventions. Third, individually identifiable health information included in the employer' s personnel records is not considered protected PHI. 81 Fourth, covered entities may disclose protected PHI to a business associate (e.g., PBM) and allow the associate to use the information on behalf of the covered entity pursuant to a written contract. Walden and Craig, in this issue of the Journal, provide a more comprehensive overview of the HIPAA legislation and regulations, particularly as they apply to health plans and PBMs. 82 Policy makers should weigh the experiences of prescription drug benefit managers in the evolving domain of patient privacy as rules are modified to meet patient needs for safety while preserving the privacy of personal health information. It is not as easy as saying that all PHI should be shared only on a needto-know basis. Yet, there is some relevance to this general dictum. The "rules of the road" for managed care pharmacists can be referenced by the acronym "TPO" to guide the use and disclosure of PHI. TPO refers to "treatment," "payment," or "operations," the permitted "uses" (internal) and "disclosures" (exter-nal) of PHI. Disclosure of PHI outside of TPO requires patientand purpose-specific authorization for this disclosure. Ultimately, the covered entity is responsible for compliance, but practically, this responsibility is transferred to the business associate (e.g., PBM) by written agreement between the covered entity and the business associate.
"Payment" includes the drug UR and UM activities performed by health plans or PBMs. Disclosure of PHI to providers by UR case managers and staff does not require patient authorization. Likewise, requests of providers for patient-specific medical record information for determinations of medical necessity do not require patient authorization. However, UR and UM personnel and operations will be held to a "minimum necessary" disclosure standard in which the requested PHI is the amount minimally necessary to fulfill obligations related to determination of medical necessity and similar language and criteria in description of benefits and summary plan documents (SPDs) of health plans. 83 The definition of minimum necessary will likely give rise to jurisprudence quicksand for health plans and in-earnest PBMs as trial lawyers strive to make cases around unnecessary privacy breaches. UR and UM personnel must navigate more perilous passage as a result of current, but still evolving, HIPAA privacy regulations.